Details

Autor(en) / Beteiligte

• Michot, Caroline
• Hubert, Laurence
• Romero, Norma B.
• Gouda, Amr
• Mamoune, Asmaa
• Mathew, Suja
• Kirk, Edwin
• Viollet, Louis
• Rahman, Shamima
• Bekri, Soumeya
• Peters, Heidi
• McGill, James
• Glamuzina, Emma
• Farrar, Michelle
• von der Hagen, Maya
• Alexander, Ian E.
• Kirmse, Brian
• Barth, Magalie
• Laforet, Pascal
• Benlian, Pascale
• Munnich, Arnold
• JeanPierre, Marc
• Elpeleg, Orly
• Pines, Ophry
• Delahodde, Agnès
• de Keyzer, Yves
• de Lonlay, Pascale

Titel

Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia

Ist Teil von

• Journal of inherited metabolic disease, 2012-11, Vol.35 (6), p.1119-1128

Ort / Verlag

Dordrecht: Springer Netherlands

Erscheinungsjahr

2012

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Background Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations. Methods Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs. Results Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3 -P24L variant. Conclusion LPIN1 -related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.